Evaluation of IV AMBTX-01 (Neridronate) for Treatment of CRPS Type 1 (CRPS-RISE)

Ambros Therapeutics, Inc.

Status and phase: Begins enrollment this month; Phase 3

Conditions: Complex Regional Pain Syndrome Type I

Treatments: Drug: Placebo; Drug: Neridronate

Study type: Interventional

Funder types: Industry

Identifiers

NCT07210515

AMBTX-01-301

Details and patient eligibility

About

Phase 3 Trial of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1

Full description

This is a multicenter, randomized, triple-blind, controlled trial, to assess the efficacy, safety, and tolerability of neridronate 400 mg IV in adult participants with the warm subtype of Complex Regional Pain Syndrome Type 1 (CRPS-1) and a positive triple phase bone scan (TPBS).

The total planned trial duration for each participant will be approximately up to 18 weeks and will include:

• Screening period of up to 6 weeks
• Treatment period on Days 1, 4, 7, and 10
• Post-treatment follow-up through week 12

Enrollment: 270 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Male or female participant ≥ 18 years of age at time of Screening.

2. A diagnosis of CRPS-1 according to the clinical Budapest Criteria as recommended by the International Association for the Study of Pain (IASP), as well as no known peripheral nerve injury. Signs and symptoms of CRPS must apply to a single identified affected limb (i.e., arm, hand, wrist, leg, ankle or foot) and must demonstrate asymmetry with respect to the contralateral limb.

3. Single affected limb at the Screening and Randomization Visits meeting the following warm subtype criteria:

   1. Edema in the affected limb

   2. AND ≥ 2 of the following:

      1. Obvious redness in the affected region relative to the same region on the contralateral limb on inspection
      2. ≥ 1°C increase in temperature on the affected limb relative to the contralateral limb
      3. Moderate-to-severe edema

4. CRPS symptoms ≤ 6 months since onset.

5. Increased uptake in the involved limb compared to the contralateral limb on TPBS (phase 2 and/or phase 3) during Screening. A historic scan not older than 3 months prior to Randomization Visit is acceptable, if available and of sufficient quality for a central read.

6. "Pain now" assessments of > 4 on the 11 point numerical rating scale in the CRPS affected limb.

7. Women of childbearing potential must:

   1. Be nonpregnant.
   2. Be nonlactating.
   3. Agree to use a highly effective method of contraception and for at least 6 months following last investigational product administration.

Exception: Women exclusively engaging in same sex sexual activities are not required to meet this criterion.

Exclusion Criteria

1. A current or prior diagnosis of CRPS Type 2 or CRPS not otherwise specified (CRPS NOS), or whose CRPS has no known inciting event, or CRPS-1 without criteria of the warm subtype at the time of Screening.
2. ≥ 40 points on the Pain Catastrophizing Scale.
3. Prior use of neridronate or participation in a clinical study where the participant may have received neridronate.
4. Participants currently taking or planning to be treated with prohibited concomitant medications/therapies, or not likely able to follow the protocol restrictions for use of concomitant treatment.
5. Severely impaired renal function.
6. Hypocalcemia.
7. Vitamin D deficiency.
8. Significant dental findings such as an unhealed tooth extraction site.
9. Eye inflammation.
10. Significantly elevated liver-related lab tests or evidence of significant liver disease.
11. Clinically unstable cardiac disease.
12. Any known conditions, from 3 months prior to Screening Visit or to the Randomization Visit, that may interfere with the assessment of CRPS-1, CRPS-related pain, safety, or other trial assessments.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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270 participants in 2 patient groups, including a placebo group

neridronate

Experimental group

Description:

400 mg AMBTX-01 infusion

Treatment:

Drug: Neridronate

Placebo

Placebo Comparator group

Description:

Placebo comparator

Treatment:

Drug: Placebo